Cytomegalovirus transmission to preterm infants during lactation.

Breastfeeding has a major impact on HCMV epidemiology. The incidence of postnatal HCMV reactivation during lactation equals the maternal seroprevalence. Infectious virus, viral DNA and RNA can be isolated easily from cell and fat-free milk whey. Early onset of viral DNAlactia and virolactia as well as high viral load in milk whey are maternal risk factors for virus transmission. The dynamics of HCMV reactivation can be described by unimodal kinetics with interindividual variation. Virus reactivation during lactation is a self-limiting local process in the absence of systemic HCMV infection. Preterm infants below 1000g birthweight and a gestational age below 30 weeks may be at high risk of acquiring a symptomatic HCMV infection. Several recent studies described low transmission rates and mostly asymptomatically infected neonates using frozen milk. Despite different freeze-storing procedures, HCMV transmissions occurred, and severe HCMV infections were observed. Few data exist on the long-term outcome of postnatally acquired HCMV infection via breast milk. To substantiate the international debate on the use of native or inactivated milk for feeding of preterm infants, additional data are necessary for better identification of mother-infant-pairs at risk for viral transmission and symptomatic infection early after birth.     

Topical Timolol for Small Hemangiomas of Infancy

Abstract: Propranolol has become the treatment of choice of large and complicated infantile hemangiomas. There is a controversy concerning the safety of systemic propranolol. Here we show that topical use of the beta‐blocker timolol can also inhibit the growth and promote regression of infantile hemangiomas. In this case series we treated 11 infantile hemangiomas in nine children including six preterm babies with the nonselective betablocker timolol. A timolol containing gel was manufactured from an ophthalmic formulation of timolol 0.5% eyedrops. This gel was applied using a standardized occlusive dressing (Finn‐Chambers) containing approximately 0.25 mg of timolol. In all infants topical timolol was associated with growth arrest, a reduction in redness and thickness within the first 2 weeks. Seven hemangiomas showed almost complete resolution, and four became much paler and thinner. No data are available on the transdermal absorption of timolol. Even supposing complete absorption of timolol from the occlusive dressing, a maximum dose of 0.25 mg of timolol would result per day and hemangioma. Regression of infantile hemangiomas treated using 0.5% timolol gel in this case series occurred earlier than spontaneous regression which is generally not observed before the age of 9–12 months. The promising results need to be verified in prospective randomized trials on topical beta blocker administration for infantile hemangiomas which should address dose, duration, and mode of application.     

Measurement of volume of cerebral blood flow in healthy preterm and term neonates with ultrasound

Changes in cerebral blood flow are important in the pathogenesis of ischaemic brain damage, but standard methods cannot measure volume of cerebral blood flow quantitatively in neonates. We used colour duplex sonography of the extracranial cerebral arteries to measure volume of global cerebral blood flow in 67 healthy preterm and term neonates. Volume of cerebral blood flow increased between the postmenstrual ages of 34 weeks (median 33 mL/min [range 23-43]) and 42 weeks (85 mL/min [57-104]). However, intersession and interobserver variability was quite large. This non-invasive method will allow quantitative bedside monitoring of global brain perfusion in preterm and term neonates with pathological disorders, and could also be used to monitor effects of neuroprotective measures.     

Development of cerebral blood flow volume in preterm neonates during the first two weeks of life

To investigate the postnatal development of cerebral perfusion in preterm neonates with normal brains over the first 2 wk of life, a prospective longitudinal study was designed. Quantitative measurement of cerebral blood flow (CBF) volume was performed using ultrasound flowmetry of the extracranial, brain-feeding arteries in 32 preterm infants of 28-35 wk gestational age. Measurements were done in the internal carotid and vertebral arteries of both sides on d 1, 2, 3, 7, and 14 after birth. A 10.0-MHz linear transducer of a computed sonography system (Acuson 128/XP10) was used. Intravascular flow volumes were calculated as the product of angle-corrected time-averaged flow velocity and the cross-sectional area of the vessel. Mean CBF volume increased markedly over the first 2 wk. One-third of this rise already occurred from the first to the second postnatal day, thereafter there was a continuous increase from d 2 to d 14 of life. Whereas the absolute level of CBF volume was primarily determined by postmenstrual age, the pattern of postnatal changes in CBF volume was found to be independent of gestational age. Arterial carbon dioxide tension, mean arterial blood pressure, and hematocrit had no influence on the development of CBF volume. The pronounced increase of CBF volume from d 1 to d 2 is likely to represent a normal adaptive response of the cerebral circulation to postnatal life. The data presented here may serve as the basis for further studies to investigate whether deviations from this adaptive response are associated with an increased risk of brain injury.     

Cytomegalovirus (CMV) inactivation in breast milk: reassessment of pasteurization and freeze-thawing

Breast-feeding mothers frequently transmit cytomegalovirus (CMV) to preterm infants of very low birth weight. Current recommendations for prevention of virus transmission are based on data published 20 y ago in the context of human milk banking. Two recent clinical trials examined storage of breast milk at -20 degrees Celsius to reduce virus transmission. However, in both studies, CMV transmission occurred. Using sensitive tools like quantitative PCR, CMV pp67 late mRNA assay, and a high-speed, centrifugation-based microculture assay for quantification of CMV infectivity, we reassessed the virological and biochemical characteristics of freeze-storing breast milk at -20 degrees Celsius, compared it with traditional Holder pasteurization (30 min at 62.5 degrees Celsius), and a new short-term pasteurization (5 s at 72 degrees Celsius) based on the generation of a milk film. Both heat treatment procedures were able to destroy viral infectivity and pp67 RNA completely. Preliminary results showed short-term heat inactivation below 72 degrees Celsius was less harmful in reducing the activity of marker enzymes than Holder pasteurization. Freezing breast milk preserved the biochemical and immunologic quality of the milk; however, late viral RNA and viral infectivity was also preserved. Compared with viral DNA, CMV-RNA more directly reflects infectious CMV in human milk samples. Further studies are necessary to evaluate short-term heat treatment below 72 degrees Celsius as an effective tool for prevention of CMV transmission.     

Postnatally acquired cytomegalovirus infection via breast milk: effects on hearing and development in preterm infants

BACKGROUND: In preterm infants there is a high risk of transmission of cytomegalovirus (CMV) via breast milk from seropositive mothers with reactivation of the virus during lactation. There is little information about the long term sequel of early postnatally acquired CMV infection in pre-term infants. This study aimed to investigate whether there was an increased frequency of impaired neurodevelopmental outcome and sensorineural hearing loss in preterm infants with postnatally acquired CMV infection through transmission by CMV-positive breast milk. METHODS: Twenty-two preterm infants [median birth weight, 1020 g (range, 600 to 1870 g); median gestational age, 27.6 weeks (range, 23.6 to 32 weeks] with early postnatally acquired CMV infection by breast-feeding (onset of viruria between Days 23 and 190 postnatally) were compared with 22 CMV-negative preterm infants individually matched for gestational age, birth weight, gender, intracranial hemorrhage and duration of ventilation. At 2 to 4.5 years of age, follow-up assessments were conducted consisting of neurologic examination, neurodevelopmental assessment and detailed audiologic tests. RESULTS: None of the children had sensorineural hearing loss. There was no difference between the groups with regard to neurologic, speech and language or motor development. CONCLUSION: The results of this study suggest that early postnatally acquired CMV infection via CMV-positive breast milk does not have a negative effect on neurodevelopment and hearing in this group of patients. Because we studied a small number of infants, further follow-up studies are warranted in preterm infants with early postnatally acquired CMV infection.     

Surveillance of Pseudomonas aeruginosa-isolates in a neonatal intensive care unit over a one year-period

Outbreaks of gram-negative bacteria such as Pseudomonas aeruginosa in neonatal intensive care units (NICU) can be life-threatening to pre-term infants, which are highly susceptible to serious infections with bacteria. Forty-two ventilated neonates in the NICU of the University Children's Hospital of Tuebingen were found to be colonized (n = 40) or infected (n = 2) with P. aeruginosa within a sampling period of one year. To investigate the colonization patterns and identify potential outbreak sources, epidemiological investigations, environmental surveillance and typing by serotyping and pulsed-field gel electrophoresis of the recovered isolates were performed. The investigation demonstrated a genetically related cluster of P. aeruginosa isolates during the surveillance period in 39 neonates and a second cluster at the end of the period in two neonates. A third strain representing a genetically distinct group was found in only one patient. Environmental investigations demonstrated the presence of P. aeruginosa in the ventilation equipment of 22 patients: binasal prongs (n = 22), water reservoir (n = 9), and heater (n = 1). In one case, P. aeruginosa was found in breast milk. Other environmental investigations revealed no P. aeruginosa. Although no evidence for a unique source was found, a series of intervention steps were initiated by the NICU personnel, medical microbiologists and infection control experts. The intervention steps included reinforced training of health care staff and a change from chemical to thermal disinfection of binasal prongs. Implementation of these measurements successfully stopped the recurrent occurrence of P. aeruginosa colonization.     

Treatment strategies for bronchopulmonary dysplasia with postnatal corticosteroids in Europe: the EURAIL survey

AIM: To survey practices in 14 European countries and describe strategies for the prevention and treatment of bronchopulmonary dysplasia with postnatal steroids (PNS). METHODS: In 1999-2000 questionnaires covering the use of PNS were sent to every neonatal unit taking very preterm newborns in charge, in population-based areas covering at least 20000 births annually. One questionnaire was sent to surveyed unit. The participating areas were chosen by an expert from each country participating in the Europe Against Immature Lung (EURAIL) study group. RESULTS: Responses to 331 questionnaires were received; the mean response rate by countries was 84% (range 64-100%). Teaching hospitals accounted for 19% of the responding units. The number of extremely premature newborns (less than 28 wk of gestation) admitted yearly to these units was 0 in 16%, < 20 in 62%, 20-39 in 11% and > 39 in 11%. Overall, 67% of the centres used PNS: 48% initiated treatment in non-intubated infants and 53% at 7-14 d. Treatment duration was 4-15 d in 62% and > 15 d in 21%. PNS administration was limited to intubated infants less often in smaller units [odds ratio (OR) 0.2, 95% confidence interval (95% CI) 0.1-0.6] and more often in non-teaching hospitals (OR 2.5, 95% CI 2.5-5.0). CONCLUSIONS: Although PNS have important side effects, they were still widely used in 1999 to treat or prevent chronic lung disease. Surprisingly, steroids are still prescribed in non-ventilated infants. PNS use should be based on guidelines derived from the evidence from randomized controlled trials. This evidence should be regularly updated and disseminated.